The present invention relates to novel physiologically active substances which are produced by a microorganism belonging to the genus Mollisia, a process for preparing the same and a pharmaceutical composition containing the same.
As the substances having a vasodilative activity which are produced by microorganisms, there are known WS-1228A and WS-1228B which are produced by Streptomyces aureofaciens [J. Antibiotics, 35, 151-156 and 157-163 (1982)]; K-259-2 produced by a microorganism belonging to the genus Micromonospora (Japanese Published Unexamined Patent application No. 63289/86), KS-619-1 produced by a microorganism belonging to the genus Streptomyces (Japanese Published Unexamined Patent Application No. 96987/86), etc. The substances of the present invention having a vasodilative activity are quite different from these substances in structure. Furthermore, no report has been made on substances having a vasodilative activity which are produced by a microorganism belonging to the genus Mollisia.
As the substances having an activity to inhibit histamine secretion which are produced by microorganisms, there are known K-252a [Jpn. J. Pharmacol., 43, 202 (1987)] and KT5556 (Japanese Published Unexamined Patent Application No. 176531/86), which are produced by a microorganism belonging to the genus Nocardiopsis. The substance of the present invention having an activity to inhibit histamine secretion is quite different from these substances in structure. Furthermore, no report has been made on substances having an activity to inhibit histamine secretion which are produced by a microorganism belonging to the genus Mollisia.
Products of a large number of microorganisms isolated from natural habitants have been studied with a view to providing useful novel physiologically active substances which can be used as pharmaceuticals or intermediates therefore. As a result, it has been found that substances having a vasodilative activity and a substance having an activity to inhibit histamine secretion are produced in the culture of a newly isolated microorganism. After isolation and purification of the substances from the culture, their physiochemical properties have been investigated, whereby the substances have been found to be novel physiologically active substances. The substances are hereinafter referred to as KS-504a, KS-504b, KS-504d and KS-504e.